Vasculogenic mimicry (VM) describes a process by which cancer cells establish an alternative perfusion pathway in an endothelial cell-free manner. Despite its strong correlation with reduced patient survival, controversy still surrounds the existence of an in vitro model of VM. Furthermore, many studies that claim to demonstrate VM fail to provide solid evidence of true hollow channels, raising concerns as to whether actual VM is actually being examined. Herein, we provide a standardized in vitro assay that recreates the formation of functional hollow channels using ovarian cancer cell lines, cancer spheres and primary cultures derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction, fluorescence confocal microscopy and dye microinjection conclusively confirm the existence of functional glycoprotein-rich lined tubular structures in vitro and demonstrate that many of structures reported in the literature may not represent VM. This assay may be useful to design and test future VM-blocking anticancer therapies.

This work is devoted to studying the influence of chamber response functions on the standard IMRT verification for the different detector technologies available on commercial devices. We have tested three of the most used 2D detector arrays for radiotherapy dosimetry verification, based on air-ionization chambers and diode detectors. The response function has been carefully simulated using the Monte Carlo method and measured through slit and pinhole collimators. Although the response function of air-ionization detectors is considerably different with respect to that of standard diodes, the impact on a verification based in the gamma function with tolerances 3 mm and 3% is quite limited. The results show that the standard air-ionization detector arrays perform in a similar way whenever the tolerances for the gamma function are not lowered below 1.5 mm and 1.5%. Additionally, the sensitivity of these devices to fluence perturbations was measured by intentionally modifying some leaf positions in the multileaf collimator. The wider response function of air-ionization chamber arrays made them slightly more sensitive to random fluence perturbations, although silicon diode arrays are more accurate to describe the dose distribution in a point by point basis.

The results indicate that the helical field deliveries in this study (including two clinical fields) do not introduce changes on the ion chamber correction factors for dosimetry. For those two specific clinical cases, ratios of chamber readings accurately represent field output factors. The values observed here for intermediate calibration fields are in agreement with previously published data based on alanine dosimetry but differ from values recently reported obtained via radiochromic dosimetry.

In this work we present the design, characterization and first clinical tests of an in-house developed two-dimensional liquid-filled ionization chamber prototype for the verification of small radiotherapy fields and treatments containing such small fields as in radiosurgery, which consists of 2 mm × 2 mm pixels arranged on a 16×8 rectangular grid. The ionization medium is isooctane. The characterization of the device included the study of depth, field-size and dose-rate dependences, which are sufficiently moderate for a good operation at therapy radiation levels. However, the detector presents an important anisotropic response, up to ≃ 12% for front versus near-lateral incidence, which can impact the verification of full treatments with different incidences. In such a case, an anisotropy correction factor can be applied. Output factors of small square fields measured with the device show a small systematic over-response, less than 1%, when compared to unshielded diode measurements. An IMRT radiosurgery treatment has been acquired with the liquid-filled ionization chamber device and compared with film dosimetry by using the gamma method, showing good agreement: over 99% passing rates for 1.2% and 1.2 mm for an incidence-per-incidence analysis; 100% passing rates for tolerances 1.8% and 1.8 mm when the whole treatment is analysed and the anisotropy correction factor is applied. The point dose verification for each incidence of the treatment performed with the liquid-filled ionization chamber agrees within 1% with a CC01 ionization chamber. This prototype has shown the utility of this kind of technology for the verification of small fields/treatments. Currently, a larger device covering a 5 cm × 5 cm area is under development.

The purpose of this work is to calculate individualized dose distributions in patients undergoing 18 F-FDG PET/CT studies through a methodology based on full Monte Carlo (MC) simulations and PET/CT patient images, and to compare such values with those obtained by employing nonindividualized phantom-based methods. Methods: We developed a MC-based methodology for individualized internal dose calculations, which relies on CT images (for organ segmentation and dose deposition), PET images (for organ segmentation and distributions of activities), and a biokinetic model (which works with information provided by PET and CT images) to obtain cumulated activities. The software vGATE version 8.1. was employed to carry out the Monte Carlo calculations. We also calculated deposited doses with nonindividualized phantom-based methods (Cristy-Eckerman, Stabin, and ICRP-133).

This method could be implemented in TPS in order to calculate dosimetry correction factors when an experimental IMRT treatment verification with in-phantom ionization chamber is performed. The miss-response of the IC due to the nonreference conditions could be quickly corrected by this method rather than employing MC derived correction factors. This method can be considered as an alternative to the plan-class associated correction factors proposed recently as part of an IAEA work group on nonstandard field dosimetry.

The differences found between overall correction factors associated with the proposed intermediate calibration fields and the clinical fields under investigation show that depending on the clinical field and the detector used, either a machine-specific reference field or a plan-class specific reference field is more representative for the clinical field. Given the experimental and numerical uncertainties and the small number of clinical fields considered in this study the significance of these observations is limited and it remains unclear for the CyberKnife if there would be a significant gain in using a pcsr field rather than a msr field as reference field for relative dosimetry.

There is increasing evidence that high doses of radiotherapy, like those delivered in stereotactic body radiotherapy (SBRT), trigger indirect mechanisms of cell death. Such effect seems to be two-fold. High doses may trigger an immune response and may cause vascular damage, leading to cell starvation and death. Development of mathematical response models, including indirect death, may help clinicians to design SBRT optimal schedules. Despite increasing experimental literature on indirect tumor cell death caused by vascular damage, efforts on modeling this effect have been limited. In this work, we present a biomathematical model of this effect. In our model, tumor oxygenation is obtained by solving the reactiondiffusion equation; radiotherapy kills tumor cells according to the linear-quadratic model, and also endothelial cells (EC), which can trigger loss of functionality of capillaries. Capillary death will affect tumor oxygenation, driving nearby tumor cells into severe hypoxia. Capillaries can recover functionality due to EC proliferation. Tumor cells entering a predetermined severe hypoxia status die according to a hypoxia-death model. This model fits recently published experimental data showing the effect of vascular damage on surviving fractions. It fits surviving fraction curves and qualitatively reproduces experimental values of percentages of functional capillaries 48 hours postirradiation, and hypoxic cells pre-and 48 hours postirradiation. This model is useful for exploring aspects of tumor and EC response to radiotherapy and constitutes a stepping stone toward modeling indirect tumor cell death caused by vascular damage and accounting for this effect during SBRT planning.Significance: A novel biomathematical model of indirect tumor cell death caused by vascular radiation damage could potentially help clinicians interpret experimental data and design better radiotherapy schedules.