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The use of MRI in radiotherapy planning and simulation is increasing rapidly and is beginning to be integrated into the external beam radiation therapy (EBRT) treatment process. Some have suggested that integrated MRI-linac systems, not the standalone MRI-Sim, represents the future of MRI in radiotherapy, and this is the claim debated in this month's Point/Counterpoint. This article is protected by copyright. All rights reserved.

Purpose: A susceptible-infected-susceptible (SIS) epidemic model was applied to radiation therapy (RT) treatments to predict morphological variations in head and neck (H&N) anatomy. Methods: 360 daily MVCT images of 12 H&N patients treated by tomotherapy were analyzed in this retrospective study. Deformable image registration (DIR) algorithms, mesh grids, and structure recontouring, implemented in the RayStation treatment planning system (TPS), were applied to assess the daily organ warping. The parotid's warping was evaluated using the epidemiological approach considering each vertex as a single subject and its deformed vector field (DVF) as an infection. Dedicated IronPython scripts were developed to export daily coordinates and displacements of the region of interest (ROI) from the TPS. matlab tools were implemented to simulate the SIS modeling. Finally, the fully trained model was applied to a new patient. Results: A QUASAR phantom was used to validate the model. The patients’ validation was obtained setting 0.4 cm of vertex displacement as threshold and splitting susceptible (S) and infectious (I) cases. The correlation between the epidemiological model and the parotids’ trend for further optimization of alpha and beta was carried out by Euclidean and dynamic time warping (DTW) distances. The best fit with experimental conditions across all patients (Euclidean distance of 4.09 ± 1.12 and DTW distance of 2.39 ± 0.66) was obtained setting the contact rate at 7.55 ± 0.69 and the recovery rate at 2.45 ± 0.26; birth rate was disregarded in this constant population. Conclusions: Combining an epidemiological model with adaptive RT (ART), the authors’ novel approach could support image-guided radiation therapy (IGRT) to validate daily setup and to forecast anatomical variations. The SIS-ART model developed could support clinical decisions in order to optimize timing of replanning achieving personalized treatments.

Purpose: Flattening filter free (FFF) beams generated by medical linear accelerators are today clinically used for stereotactical and non-stereotactical radiotherapy treatments. Such beams differ from the standard flattened beams (FF) in the high dose rate and the profile shape peaked on the beam central axis. Definition of new parameters as unflatness and slope for FFF beams has been proposed based on a renormalization factor for FFF profiles. The present study aims to assess the dosimetric differences between FFF beams generated by linear accelerators from different vendors, and to provide renormalization and parameter data of the two kinds of units. Methods: Dosimetric data from two Varian TrueBeam and two Elekta Versa HD linear accelerators, all with 6 and 10 MV nominal accelerating potentials, FF and FFF modes have been collected. Renormalization factors and related fit parameters according to Fogliata et al. [“Definition of parameters for quality assurance of flattening filter free (FFF) photon beams in radiation therapy,” Med. Phys. 39, 6455–6464 (2012)] have been evaluated for FFF beams of both units and energies. Unflatness and slope parameters from profile curves were evaluated. Dosimetric differences in terms of beam penetration and near-the-surface dose were also assessed. Results: FFF profile parameters have been updated; renormalization factors and unflatness from the Varian units are consistent with the published data. Elekta FFF beam qualities, different from the Varian generated beams, tend to express similar behaviour as the FF beam of the corresponding nominal energy. TPR20,10 for 6 and 10 MV FF and FFF TrueBeam beams are 0.665, 0.629 (6 MV) and 0.738, 0.703 (10 MV). The same figures for Versa HD units are 0.684, 0.678 (6 MV) and 0.734, 0.721 (10 MV). Conclusions: Renormalization factor and unflatness parameters evaluated from Varian and Elekta FFF beams are provided, in particular renormalization factors table and fit parameters.

Purpose: Due to the potentially periodic collimator dynamic in volumetric modulated arc therapy (VMAT) dose deliveries with the sweeping-window arc therapy (SWAT) technique, additional manifestations of dosimetric deviations in the presence of intrafractional motion may occur. With a fast multileaf collimator (MLC), and a flattening filter free dose delivery, treatment times close to 60 s per fraction are clinical reality. For these treatment sequences, the human breathing period can be close to the collimator sweeping period. Compared to a random arrangement of the segments, this will cause a further degradation of the dose homogeneity. Methods: Fifty VMAT sequences of potentially moving target volumes were delivered on a two dimensional ionization chamber array. In order to detect interplay effects along all three coordinate axes, time resolved measurements were performed twice—with the detector aligned in vertical (V) or horizontal (H) orientation. All dose matrices were then moved within a simulation software by a time-dependent motion vector. The minimum relative equivalent uniform dose EUD r,m for all breathing starting phases was determined for each amplitude and period. Furthermore, an estimation of periods with minimum EUD was performed. Additionally, LINAC logfiles were recorded during plan delivery. The MLC, jaw, gantry angle, and monitor unit settings were continuously saved and used to calculate the correlation coefficient between the target motion and the dose weighed collimator motion component for each direction (CC, LR, AP) separately. Results: The resulting EUD r,m were EUD r,m (CC V ) = (98.3 ± 0.6)%, EUD r,m (CC H ) = (98.6 ± 0.5)%, EUD r,m (AP V ) = (97.7 ± 0.9)%, and EUD r,m (LR H ) = (97.8 ± 0.9)%. The overall minimum relative EUD observed for 360∘ arc midventilation treatments was 94.6%. The treatment plan with the shortest period and a minimum relative EUD of less than 97% was found at T = 6.1 s. For a partial 120∘ arc, an EUD r,m = 92.0% was found. In all cases, a correlation coefficient above 0.5 corresponded to a minimum in EUD. Conclusions: With the advent of fast VMAT delivery techniques, nonrobust treatment sequences for human breathing patterns can be generated. These sequences are characterized by a large correlation coefficient between a target motion component and the corresponding collimator dynamic. By iteratively decreasing the maximum allowed dose rate, a low correlation coefficient and consequentially a robust treatment sequence are ensured.

Purpose: Pencil-beam (PB) based dose calculation for treatment planning is limited by inaccuracies in regions of tissue inhomogeneities, particularly in situations with lateral electron disequilibrium as is present at tissue/lung interfaces. To overcome these limitations, a new “lateral disequilibrium inclusive” (LDI) PB based calculation algorithm was introduced. In this study, the authors evaluated the accuracy of the new model by film and ionization chamber measurements and Monte Carlo simulations. Methods: To validate the performance of the newLDI algorithm implemented in Corvus 09®, eight test plans were generated on inhomogeneous thorax and pelvis phantoms. In addition, three plans were calculated with a simple effective path length (EPL) algorithm on the inhomogeneous thorax phantom. To simulate homogeneous tissues, four test plans were evaluated in homogeneous phantoms (homogeneous dose calculation). Results: The mean pixel pass rates and standard deviations of the gamma 4%/4 mm test for the film measurements were ( 96 ± 3 ) % for the plans calculated with LDI, ( 70 ± 5 ) % for the plans calculated with EPL, and ( 99 ± 1 ) % for the homogeneous plans. Ionization chamber measurements and Monte Carlo simulations confirmed the high accuracy of the new algorithm (dose deviations ≤ 4 % ; gamma 3%/3 mm ≥ 96 % ) Conclusions: LDI represents an accurate and fast dose calculation algorithm for treatment planning.

With an incidence of 15/105 in the general population, brain metastases constitute a serious, debilitating complication in cancer patients. The majority of those patients suffer from more than one metastasis, but up to 30% to 40% present with a solitary lesion. Whole-brain radiotherapy (WBRT) extends median survival from 1 to 2 months for treatment with steroids only, to 4 to 6 months in most series. However, long-term survival (>1–2 years) is observed in up to 10% of patients with favorable prognostic factors, such as solitary lesions, good Karnofsky performance status, and absence of extracranial disease. For those patients, individually optimized treatment is worthwhile. For good-prognosis patients with controlled extracranial disease, surgery in combination with postoperative WBRT should be considered, especially when fast relief of symptoms is mandated. For surgically inaccessible solitary lesions below a size threshold of approximately 30 ccm, stereotactic radiosurgery (RS), although never compared to surgery in a randomized fashion, seems to yield comparable results and is the treatment of choice for more than one lesion in appropriately selected patients. Nevertheless, a number of questions concerning the optimal treatment regimens for brain metastases remain. These mainly concern the radiation dose, need for a combination of RS and WBRT, relative timing of different treatment modalities, and maximum number of brain metastases that can reasonably be treated with RS when long-term progression-free survival is the goal. However, RS is definitely an excellent option for salvage and palliation in patients with short life expectancy, as it is simultaneously noninvasive and cost-effective, with short hospitalization times. Semin. Surg. Oncol. 20:50–56, 2001. © 2001 Wiley-Liss, Inc.

PC10 is a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The staining pattern in immunochemistry depends on fixation and detergent extraction treatment. The aim of this study was to validate the flow cytometric PCNA assay against Bromodeoxyuridine-labelling index (BrdUrd-LI) under different proliferative conditions in vitro. Expression of PCNA in methanol fixed cells with, and without, prior detergent extraction with EDTA/Triton was compared to BrdUrd-labelling index in NIH-3T3 fibroblasts and human Caski tumour cells in exponential phase and under confluent conditions. Serum stimulation and serum starvation conditions were studied. The results for BrdUrd-LI and PCNA-index after extraction showed good correlation for 3T3 fibroblasts and for Caski cells, with some differences for serum withdrawn Caski cells. There was no correlation between the number of cells that were positive for PCNA without extraction and BrdUrd-LI. Spheroid cells with G1-DNA-content showed an almost synchronous recruitment and progression through the cell cycle after trypsination and replating. Tightly bound PCNA paralleled this synchronicity whereas total PCNA did not change significantly. The results demonstrate that immunochemical detection of non-extractable PCNA-index gives similar results as compared with BrdUrd-labelling index under different proliferative conditions in vitro for different monolayer cell lines, whereas without extraction PCNA does not correlate with BrdUrd-LI in these fast growing cell lines due to its long half-life. PCNA expression parallels the progression through the cell cycle in V79 spheroids, a primitive model of tumour growth.

Purpose: This project presents an analysis of the point spread function (PSF) of isocentric digital tomosynthesis (DTS). DTS is a limited angle 3‐ dimensional reconstruction from cone beam projections, with high resolution for excellent imaging of both bony anatomy and soft tissue. Its major application is on‐board imaging. The scans can be acquired during a single breath hold, thus eliminating respiratory motion artifacts without gating techniques. Method and Materials: The geometry of a linear accelerator (Clinac 21EX from Varian) equipped with a kV on‐board imager and CBCT capability was used. We simulated projection data sets of a single point source (PS) for different total scan angles from 26° to 58°. The PS was located along the horizontal axis through the isocenter from the kV x‐ray source to the detector (z‐axis). DTS reconstructions were generated from the simulated projections, using a standard Feldkamp technique. The full width at half maximum (FWHM) of the resulting PSF was computed along the z‐direction in stacks of DTS slices. Results: The PSF shows a bow‐tie shape in the z‐direction. The spread of the blurring function increases for larger scan angles. Furthermore, the FWHM decreases as both distance from the detector and the scan angle increase. FWHM values ranged from ∼2.5mm to ∼5mm near the kV source, and from ∼5mm to ∼11mm near the detector, as the scan angle was varied. For a typical 44∼ scan, the FWHM varied from ∼3mm when the PS was moved 20cm towards the source away from the isocenter, to ∼6mm when was moved 24cm towards the detector.Conclusion: The blurring effect of isocentric DTS is dependent on the total scan angle and the point of interest. These characteristics will provide guidance to imaging techniques using DTS for clinical applications. This project is partially supported by Varian Medical System.