Electron beam collimation with a photon MLC for standard electron treatments.

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair.

The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced - and thus mechanically tailored - hydrogels for IVD repair.

The BMP2 variant L51P restores the osteogenic differentiation of human mesenchymal stromal cells in the presence of intervertebral disc cells.

Spinal fusion is hampered by the presence of remaining intervertebral disc (IVD) tissue and leads to spinal non-union. While the exact mechanism remains unknown, we hypothesise that factors preventing disc ossification, such as antagonists of the bone morphogenetic proteins (BMP), could be responsible for this process. The objective of this study was to investigate spinal non-union using an in vitro human model with a focus on the BMP signalling components and to identify factors contributing to the incomplete and delayed ossification. Human bone marrow-derived mesenchymal stromal cells (MSC) were cocultured with IVD cells in the presence of L51P, a BMP2 variant with osteoinductive potential. The ossification of MSC was evaluated by quantitative reverse transcription polymerase chain reaction (qPCR), alkaline phosphatase (ALP) activity and alizarin red staining. Endogenous expression of major BMP antagonists, namely Gremlin (GREM1), Noggin (NOG) and Chordin (CHRD) was detected in IVD-derived cells, with abundance in nucleus pulposus cells. Osteogenesis of MSC was hindered by IVD cells as shown by reduced alizarin red staining, ALP activity and qPCR. L51P, added to the cocultures, restored mineralisation, blocking the activity of the BMP antagonists secreted by IVD cells. It is possible that the BMP antagonists secreted by IVD cells are responsible for spinal non-unions. The inhibition of BMP antagonists with L51P may result in an efficient and more physiological osteoinduction rather than delivery of exogenous osteogenic factors. Therefore, L51P might represent an attractive therapeutic candidate for bone healing.

Assessing dose rate distributions in VMAT plans.

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within ±0.4 s and doses ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min(-1) for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min(-1) for conventional fractionation.

SU-E-T-507: Dose Calculation Quality of AcurosXB Involving a HD120 MLC Compared with Monte Carlo Methods.

PURPOSE: Advanced radiation therapy requires highly sophisticated dose calculation algorithms such as finite element based Boltzmann solvers or Monte Carlo (MC) methods. MC is commonly accepted as the golden standard method for dose calculation in high energy treatments and thus it is used for benchmarking other algorithms. In this work the quality of dose distribution calculated using the Boltzmann solver based AcurosXB algorithm within Eclipse (Varian Medical Systems) is investigated for volumetric modulated arc treatment (VMAT) plans involving the high definition MLC (HD120 MLC) by comparing doses with the validated Swiss Monte Carlo Plan (SMCP). MATERIALS & METHODS: Within SMCP and Eclipse using AcurosXB, 10 VMAT H&N patient plans and corresponding verification plans were recalculated using fixed MUs. In SMCP, radiation transport and dose calculation were performed using VMC++ with a statistical uncertainty of 1%. The voxel size was 2.5 mm for SMCP and AcurosXB and the same material composition data was used for CT conversion. Dose volume histograms (DVH) were used in order to quantify the difference between the dose distributions of the patient plans. In addition, calculated verification plans were compared with measurements carried out with the Delta4 system (Scandidos) by using the gamma evaluation with 3%/3 mm criteria of points having a dose larger than 20% of isocenter dose. RESULTS: DVHs for the patient plans showed good agreement between SMCP and AcurosXB calculations. Overall AcurosXB lead to an underestimation of the median dose values by about 1%. For measured total dose distributions of the verification plans on average 98.6% and 99.0% of the points fullfil the gamma criteria for the dose calculated using AcurosXB and SMCP, respectively. CONCLUSIONS: Resulting AcurosXB dose distributions for VMAT H&N plans involving a HD120 MLC are in good agreement with calculated SMCP dose distributions. CONFLICT OF INTEREST: This work was supported by Varian Medical Systems.