Araceli Gago-Arias

Correction factors for A1SL ionization chamber dosimetry in TomoTherapy: Machine‐specific, plan‐class, and clinical fields

PURPOSEnRecently, an international working group on nonstandard fields presented a new formalism for ionization chamber reference dosimetry of small and nonstandard fields [Alfonso et al., Med. Phys. 35, 5179-5186 (2008)] which has been adopted by AAPM TG-148. This work presents an experimental determination of the correction factors for reference dosimetry with an Exradin A1SL thimble ionization chamber in a TomoTherapy unit, focusing on: (i) machine-specific reference field, (ii) plan-class-specific reference field, and (iii) two clinical treatments.nnnMETHODSnIonization chamber measurements were performed in the TomoTherapy unit for intermediate (machine-specific and plan-class-specific) calibration fields, based on the reference conditions defined by AAPM TG-148, and two clinical treatments (lung and head-and-neck). Alanine reference dosimetry was employed to determine absorbed dose to water at the point of interest for the fields under investigation. The corresponding chamber correction factors were calculated from alanine to ionization chamber measurements ratios.nnnRESULTSnTwo different methods of determining the beam quality correction factor k(Q,Q(0) ) for the A1SL ionization chamber in this TomoTherapy unit, where reference conditions for conventional beam quality determination cannot be met, result in consistent values. The observed values of overall correction factors obtained for intermediate and clinical fields are consistently around 0.98 with a typical expanded relative uncertainty of 2% (ku2009=u20092), which when considered make such correction factors compatible with unity. However, all of them are systematically lower than unity, which is shown to be significant when a hypothesis test assuming a t-student distribution is performed (p=1.8×10(-2)). Correction factors k(Q(clin),Q(pcsr) ) (f(clin),f(pcsr) ) and k(Q(clin),Q(msr) ) (f(clin),f(msr) ), which are needed for the computation of field factors for relative dosimetry of clinical beams, have been found to be very close to unity for two clinical treatments.nnnCONCLUSIONSnThe 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.

Evaluation of chamber response function influence on IMRT verification using 2D commercial detector arrays

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.

A two-dimensional liquid-filled ionization chamber array prototype for small-field verification: characterization and first clinical tests.

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 2xa0mm × 2xa0mm 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 1.2xa0mm for an incidence-per-incidence analysis; 100% passing rates for tolerances 1.8% and 1.8xa0mm 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 5xa0cm × 5xa0cm area is under development.

Correction factors for ionization chamber dosimetry in CyberKnife: Machine‐specific, plan‐class, and clinical fields

PURPOSEnThe aim of this work is the application of the formalism for ionization chamber reference dosimetry of small and nonstandard fields [R. Alfonso, P. Andreo, R. Capote, M. S. Huq, W. Kilby, P. Kjäll, T. R. Mackie, H. Palmans, K. Rosser, J. Seuntjens, W. Ullrich, and S. Vatnitsky, A new formalism for reference dosimetry of small and nonstandard fields, Med. Phys. 35, 5179-5186 (2008)] to the CyberKnife robotic radiosurgery system. Correction factors for intermediate calibration fields, a machine-specific reference field (msr) and two plan-class specific reference fields (pcsr), have been studied. Furthermore, the applicability of the new formalism to clinical dosimetry has been analyzed through the investigation of two clinical treatments.nnnMETHODSnPTW31014 and Scanditronix-Wellhofer CC13 ionization chamber measurements were performed for the fields under investigation. Absorbed dose to water was determined using alanine reference dosimetry, and experimental correction factors were calculated from alanine to ionization chamber readings ratios. In addition, correction factors were calculated for the intermediate calibration fields and one of the clinical treatment fields using the Monte Carlo method and these were compared with the experimental values.nnnRESULTSnOverall correction factors deviating from unity by approximately 2% were obtained from both measurements and simulations, with values below and above unity for the studied intermediate calibration fields and clinical fields for the ionization chambers under consideration. Monte Carlo simulations yielded correction factors comparable with those obtained from measurements for the machine-specific reference field, although differences from 1% to 3.3% were observed between measured and calculated correction factors for the composite intermediate calibration fields. Dose distribution inhomogeneities are thought to be responsible for such discrepancies.nnnCONCLUSIONSnThe 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.

eIMRT: a web platform for the verification and optimization of radiation treatment plans

The eIMRT platform is a remote distributed computing tool that provides users with Internet access to three different services: Monte Carlo optimization of treatment plans, CRT & IMRT treatment optimization, and a database of relevant radiation treatments/clinical cases. These services are accessible through a user‐friendly and platform independent web page. Its flexible and scalable design focuses on providing the final users with services rather than a collection of software pieces. All input and output data (CT, contours, treatment plans and dose distributions) are handled using the DICOM format. The design, implementation, and support of the verification and optimization algorithms are hidden to the user. This allows a unified, robust handling of the software and hardware that enables these computation‐intensive services. The eIMRT platform is currently hosted by the Galician Supercomputing Center (CESGA) and may be accessible upon request (there is a demo version at http://eimrt.cesga.es:8080/eIMRT2/demo; request access in http://eimrt.cesga.es/signup.html). This paper describes all aspects of the eIMRT algorithms in depth its user interface, and its services. Due to the flexible design of the platform, it has numerous applications including the intercenter comparison of treatment planning, the quality assurance of radiation treatments, the design and implementation of new approaches to certain types of treatments, and the sharing of information on radiation treatment techniques. In addition, the web platform and software tools developed for treatment verification and optimization have a modular design that allows the user to extend them with new algorithms. This software is not a commercial product. It is the result of the collaborative effort of different public research institutions and is planned to be distributed as an open source project. In this way, it will be available to any user; new releases will be generated with the new implemented codes or upgrades. PACS number: 87.55.kh

Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death.

The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models.

Analysis of ionic mobilities in liquid isooctane with low dose radiotherapy pulsed photon beams

In this work we present a model of signal temporal development in ionization chambers and we use it to determine ionic mobilities and relative densities of charge carriers in non-ultrapure liquid isooctane using a liquid-filled ionization chamber dosimeter. The detector has been irradiated with a low dose rate, short pulsed photon beam generated with a medical LINAC. Ionic mobilities have been obtained by studying the temporal development of the readout signal and fitting it to a model for low dose rate beams where recombination is negligible. The best fit has been obtained for 3 ionic species with mobilities k1 = (2.22±0.22) × 10−8, k2 = (3.37±0.43) × 10−8, k3 = (19.69±2.59) × 10−8 m2 V−1 s−1 and relative densities n1 = 0.5 (n1 is not a fitting parameter), n2 = 0.23±0.03 and n3 = 0.27±0.03.

Structural and functional identification of vasculogenic mimicry in vitro

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.

Development of an alanine dosimetry system for radiation dose measurements in the radiotherapy range

Alanine/ESR systems provide an interesting alternative to standard dosimetry systems like solid state or gas ionization chambers for dosimetry in radiotherapy. This is primarily due to the negligible energy dependence, high stability, and the possibility of using small pellets that are especially suitable for the dosimetry of small fields. In order to obtain acceptable dose uncertainties in the radiotherapy dose range, the setup, operational parameters and quantification methods need to be carefully investigated and optimized. In this work we present the development of an alanine/ESR dosimetry system, traced to the secondary standard laboratory of absorbed dose to water at the Radiation Physics Laboratory of the Universidade de Santiago de Compostela (Spain). We focus on the setup, the optimization of the operational parameters of the ESR spectrometer, the quantification of the readout signal and the construction of a calibration curve. The evaluation of the uncertainty budget is also a key component of an alanine/ESR system for radiotherapy dosimetry, and is presented in detail.After the optimization of the procedures, we have achieved a relative uncertainty of 1.7% (k=2) for an absorbed dose of 10 Gy, decreasing to 0.9% for 50 Gy.

A Volumetric Delta TCP Tool to Quantify Treatment Outcome Effectiveness Based on Biological Parameters and Different Dose Distributions

Intra-tumor variability of oxygenation and clonogenic cell density causes tumor non-uniform spatial response to radiation. Strategies like dose redistribution/boosting, whose impact should be quantified in terms of tumor control probability (TCP), have been proposed to improve treatment outcome. In 1999, Sanchez-Nieto et al. developed a tool to evaluate the impact of dose distribution inhomogeneities, compared to a reference homogeneous dose distribution, in terms of TCP. DVH data were used to calculate the so-called ∆TCP, defined as the difference in TCP arising from dose variations in individual DVH-bins. In this work, we develop an open source tool to calculate volumetric ∆TCP and evaluate the impact on TCP of: (i) Spatial dose distribution variations with respect to a reference dose; (ii) Spatial radiosensitivity variations with respect to a reference radiosensitivity; (iii) Simultaneous variation in dose distribution and radiosensitivity. ∆TCP calculations can be evaluated voxel-by-voxel, or in a user defined subvolume basis. The tool capabilities are shown with 2 examples of H&N RT treatments and subvolume contours data providing information about tumor oxygenation status. ΔTCP values are computed for a homogeneous dose to a well oxygenated tumor volume (with a homogeneous 5% vascular fraction), as reference condition, with respect to the same dose now considering 3 oxygenation levels and 3 cell density values (104, 106 and 107 cells/mm3, respectively). ΔTCP values are also computed for the comparison of a homogenous dose distribution vs a redistributed dose distribution delivered to the non-homogeneous tumor.