News in magnetic resonance imaging use for radiation oncology.

The purpose of this article is to give a summary of the progress of magnetic resonance imaging (MRI) in radiotherapy. MRI is an important imaging modality for treatment planning in radiotherapy. However, the registration step with the simulation scanner can be a source of errors, motivating the implementation of all-MRI simulation methods and new accelerators coupled with on-board MRI. First, practical MRI imaging for radiotherapy is detailed, but also the importance of a coherent imaging workflow incorporating all imaging modalities. Second, future evolutions and research domains such as quantitative imaging biomarkers, MRI-only pseudo computed tomography and radiomics are discussed. Finally, the application of MRI during radiotherapy treatment is reviewed: the use of MR-linear accelerators. MRI is increasingly integrated into radiotherapy. Advances in diagnostic imaging can thus benefit radiotherapy, but specific radiotherapy constraints lead to additional challenges and require close collaboration between radiologists, radiation oncologists, technologists and physicists. The integration of quantitative imaging biomarkers in the radiotherapy process will result in mutual benefit for diagnostic imaging and radiotherapy. MRI-guided radiotherapy has already been used for several years in clinical routine. Abdominopelvic neoplasias (pancreas, liver, prostate) are the preferred locations for treatment because of their favourable contrast in MRI, their movement during irradiation and their proximity to organs at risk of radiation exposure, making the tracking and daily adaptation of the plan essential. MRI has emerged as an increasingly necessary imaging modality for radiotherapy planning. Inclusion of patients in clinical trials evaluating new MRI-guided radiotherapy techniques and associated quantitative imaging biomarkers will be necessary to assess the benefits.

[Radiotherapy for patients with early-stage glottic squamous cell carcinoma of the larynx: Interest of hypofractionation?] / Radiothérapie du carcinome épidermoïde du larynx de stade précoce, étage glottique : intérêt de l'hypofractionnement ?

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

Integration of the M6 Cyberknife in the Moderato Monte Carlo platform and prediction of beam parameters using machine learning.

PURPOSE: This work describes the integration of the M6 Cyberknife in the Moderato Monte Carlo platform, and introduces a machine learning method to accelerate the modelling of a linac. METHODS: The MLC-equipped M6 Cyberknife was modelled and integrated in Moderato, our in-house platform offering independent verification of radiotherapy dose distributions. The model was validated by comparing TPS dose distributions with Moderato and by film measurements. Using this model, a machine learning algorithm was trained to find electron beam parameters for other M6 devices, by simulating dose curves with varying spot size and energy. The algorithm was optimized using cross-validation and tested with measurements from other institutions equipped with a M6 Cyberknife. RESULTS: Optimal agreement in the Monte Carlo model was reached for a monoenergetic electron beam of 6.75 MeV with Gaussian spatial distribution of 2.4 mm FWHM. Clinical plan dose distributions from Moderato agreed within 2% with the TPS, and film measurements confirmed the accuracy of the model. Cross-validation of the prediction algorithm produced mean absolute errors of 0.1 MeV and 0.3 mm for beam energy and spot size respectively. Prediction-based simulated dose curves for other centres agreed within 3% with measurements, except for one device where differences up to 6% were detected. CONCLUSIONS: The M6 Cyberknife was integrated in Moderato and validated through dose re-calculations and film measurements. The prediction algorithm was successfully applied to obtain electron beam parameters for other M6 devices. This method would prove useful to speed up modelling of new machines in Monte Carlo systems.

[Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging]. / Planification de la radiothérapie du cancer de la prostate par l'imagerie par résonance magnétique.

PURPOSE: Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. MATERIALS AND METHODS: A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. RESULTS: Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. CONCLUSION: The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images.

[Left-sided breast cancer locoregional radiation therapy with rotational intensity-modulated irradiation and deep inspiration breath hold: Dosimetric comparison]. / Irradiation mammaire locorégionale gauche avec modulation d'intensité rotationnelle et inspiration profonde : comparaison dosimétrique.

PURPOSE: Adjuvant left-sided breast cancer locoregional radiotherapy can be accounted for long-term cardiac toxicity. The deep inspiration breath hold techniques can reduce cardiac doses. Only a few studies have investigated rotational intensity-modulated radiotherapy with deep inspiration breath hold. MATERIAL AND METHODS: We conducted a dosimetric study comparing rotational intensity-modulated radiotherapy in free breathing with deep inspiration breath hold for irradiation of left breast cancer and locoregional lymph nodes. Doses to organs at risk were compared, as well as doses to coronary arteries, left anterior descending coronary artery region, and aortic valve. RESULTS: The data from nine patients were included in the study. Treatment plans were comparable for target volumes. The deep inspiration breath hold delivery technique, compared with free breathing, reduced radiation dose to the heart (mean dose 4.8Gy vs. 6.6Gy, p=0.008; dose in 2% of the volume 16.8Gy vs. 23.3Gy, p=0.008; volume receiving 25Gy 0.8% vs. 2,2%, p=0.008; volume receiving 30Gy 0.4% vs. 1.2%, p=0.009), as well as to the right coronary artery (mean dose 6Gy vs. 8.9Gy, p=0.028), to the left anterior descending artery (mean dose 9.6Gy vs. 14.6Gy, p=0.021), to the left anterior descending coronary artery region (dose in 2% of the volume 17.4Gy vs. 24.6Gy, p=0.021), and to the aortic valve (mean dose 4.8Gy vs. 7Gy, p=0.028). Other doses to organs at risk were similar. CONCLUSION: Rotational intensity-modulated radiotherapy with deep inspiration breath hold is associated with better sparing of the heart, on the right and left anterior descending coronary arteries, and on the aortic valve, compared with free breathing techniques, for adjuvant left breast cancer locoregional irradiation.

Use of an in-house Monte Carlo platform to assess the clinical impact of algorithm-related dose differences on DVH constraints.

PURPOSE: The aim of the present work is to evaluate a semi-automatic prescription and validation system of treatment plans for complex delivery techniques, integrated in a Monte Carlo platform, and to investigate the clinical impact of dose differences due to the calculation algorithms, by assessing the changes in DVH constraints. METHODS: A new prescription module was implemented into the Moderato system, an in-house Monte Carlo platform, with corresponding dose constraints generated depending on the anatomical region and fractionation scheme considered. The platform was tested on 83 cases treated with Cyberknife and Tomotherapy machines, to assess whether dose variations between the re-calculated dose and the Treatment Planning System might impact the dose constraints on the sensitive structures. RESULTS: Dose differences were small (within 3%) between calculation algorithms in most of the thoracic, pelvic and abdominal cases, both for the Cyberknife and Tomotherapy machines. On the other hand, spinal and head and neck treatments presented a few significant dose deviations for constraints on small volumes, such as the optic pathways and the spinal cord. These differences range from -11% to +6%, inducing constraint violations of up to 8% over the dose limit. CONCLUSIONS: The Moderato platform offers an interesting tool for plan quality validation, with a prescription module highlighting crucial features in the structures list, and a Monte Carlo dose re-calculation for complex modern techniques. Due to the high number of warnings appearing in some situations, display optimization is required in practice.

About the non-consistency of PTV-based prescription in lung.

PURPOSE: The goal of this study is to show that the PTV concept is inconsistent for prescribing lung treatments when using type B algorithms, which take into account lateral electron transport. It is well known that type A dose calculation algorithms are not capable of calculating dose in lung correctly. Dose calculations should be based on type B algorithms. However, the combination of a type B algorithm with the PTV concept leads to prescription inconsistencies. METHODS: A spherical isocentric setup has been simulated, using multiple realistic values for lung density, tumor density and collimator size. Different prescription methods are investigated using Dose-Volume-Histograms (DVH), Dose-Mass-Histograms (DMH), generalized Equivalent Uniform Dose (gEUD) and surrounding isodose percentage. RESULTS: Isodose percentages on the PTV drop down to 50% for small tumors and low lung density. When applying the same PTV prescription to different patients with different lung characteristics, the effective mean dose to the GTV is very different, with factors up to 1.4. The most consistent prescription method seems to be the D50%DMH (PTV) DMH point, but is also limited to tumors with size over 1cm. CONCLUSIONS: Even when using the different prescription methods, the prescription to the PTV is not consistent for type B-algorithm based dose calculations if clinical studies should produce coherent data. This combination leads to patients' GTV with low lung density possibly receiving very high dose compared to patients with higher lung density. The only solution seems to remove the classical PTV concept for type B dose calculations in lung.

Clinical implementation of a Monte Carlo based treatment plan QA platform for validation of Cyberknife and Tomotherapy treatments.

PURPOSE: The main focus of the current paper is the clinical implementation of a Monte Carlo based platform for treatment plan validation for Tomotherapy and Cyberknife, without adding additional tasks to the dosimetry department. METHODS: The Monte Carlo platform consists of C++ classes for the actual functionality and a web based GUI that allows accessing the system using a web browser. Calculations are based on BEAMnrc/DOSXYZnrc and/or GATE and are performed automatically after exporting the dicom data from the treatment planning system. For Cyberknife treatments of moving targets, the log files saved during the treatment (position of robot, internal fiducials and external markers) can be used in combination with the 4D planning CT to reconstruct the actually delivered dose. The Monte Carlo platform is also used for calculation on MRI images, using pseudo-CT conversion. RESULTS: For Tomotherapy treatments we obtain an excellent agreement (within 2%) for almost all cases. However, we have been able to detect a problem regarding the CT Hounsfield units definition of the Toshiba Large Bore CT when using a large reconstruction diameter. For Cyberknife treatments we obtain an excellent agreement with the Monte Carlo algorithm of the treatment planning system. For some extreme cases, when treating small lung lesions in low density lung tissue, small differences are obtained due to the different cut-off energy of the secondary electrons. CONCLUSIONS: A Monte Carlo based treatment plan validation tool has successfully been implemented in clinical routine and is used to systematically validate all Cyberknife and Tomotherapy plans.

Treatment and technical intervention time analysis of a robotic stereotactic radiotherapy system.

The purpose of this study is to obtain a better operational knowledge of Stereotactic Body Radiotherapy (SBRT) treatments with CyberKnife(r). An analysis of both In-room Times (IRT) and technical interventions of 5 years of treatments was performed, during which more than 1600 patients were treated for various indications, including liver (21%), lung (29%), intracranial (13%), head and neck (11%) and prostate (7%). Technical interventions were recorded along with the time of the failure, time to the intervention, and the complexity and duration of the repair. Analyses of Time Between Failures (TBF) and Service Disrupting TBF(disr) were performed. Treatment time data and variability per indication and following different system upgrades were evaluated. Large variations of IRTs were found between indications, but also large variations for each indication. The combination of the time reduction Tool (using Iris(r)) and Improved Stop Handling was of major impact to shortening of treatment times. The first implementation of the Iris collimator alone did not lead to significantly shorter IRTs for us except during prostate treatments. This was mostly due to the addition at the same time of larger rotational compensation for prostate treatments (58 instead of 1.58). Significant differences of duration between the first fraction and following fractions of a treatment, representing the necessity of defining imaging parameters and explanation to patients, were found for liver (12 min) and lung treatments using Xsight(r) Spine (5 min). Liver and lung treatments represent the longest IRT's and involve the largest variability's in IRT. The malfunction rate of the system followed a Weibull distribution with the shape and scale parameters of 0.8 and 39.7. Mean TBF(disr) was 68 work hours. 60 to 80% of the service disrupting interventions were resolved within 30-60 min, 5% required external intervention and 30% occurred in the morning. The presented results can be applied in the evaluation of the required machine time in order to implement robotic radiosurgery for different indications. The analytical distributions of IRTs and technical interruptions can be used for simulations.

Use of a liquid ionization chamber for stereotactic radiotherapy dosimetry.

Liquid ionization chambers (LICs) offer an interesting tool in the field of small beam dosimetry, allowing better spatial resolution and reduced perturbation effects. However, some aspects remain to be addressed, such as the higher recombination and the effects from the materials of the detector. Our aim was to investigate these issues and their impact. The first step was the evaluation of the recombination effects. Measurements were performed at different SSDs to vary the dose per pulse, and the collection efficiency was obtained. The BEAMnrc code was then used to model the Cyberknife head. Finally, the liquid ionization chamber itself was modelled using the EGSnrc-based code Cavity allowing the evaluation of the influence of the volume and the chamber materials. The liquid ionization charge collection efficiency is approximately 0.98 at 1.5 mGy pulse(-1), the highest dose per pulse that we have measured. Its impact on the accuracy of output factors is less than half a per cent. The detector modelling showed a significant contribution from the graphite electrode, up to 6% for the 5 mm collimator. The dependence of the average electronic mass collision stopping power of iso-octane with beam collimation is negligible and thus has no influence on output factor measurements. Finally, the volume effect reaches 5% for the small 5 mm collimator and becomes much smaller (<0.5%) for diameters above 10 mm. LICs can effectively be used for small beam relative dosimetry as long as adequate correction factors are applied, especially for the electrode and volume effects.

The influence of small field sizes, penumbra, spot size and measurement depth on perturbation factors for microionization chambers.

The purpose of this study was the investigation of perturbation factors for microionization chambers in small field dosimetry and the influence of penumbra for different spot sizes. To this purpose, correlated sampling was implemented in the EGSnrc Monte Carlo (MC) user code cavity: CScavity. CScavity was first benchmarked against results in the literature for an NE2571 chamber. An efficiency increase of 17 was attained for the calculation of a realistic chamber perturbation factor in a water phantom. Calculations have been performed for microionization chambers of type PinPoint 31006 and PinPoint 31016 in full BEAMnrc linac simulations. Investigating the physical backgrounds of the differences for these small field settings, perturbation factors have been split up into (1) central electrode perturbation, (2) wall perturbation, (3) air-to-water perturbation (chamber volume air-to-water) and (4) water volume perturbation (water chamber volume to 1 mm(3) voxel). The influence of different spot sizes, position in penumbra, measuring depth and detector geometry on these perturbation factors has been investigated, in a 0.8 x 0.8 cm(2) field setting. p(cel) for the PP31006 steel electrode shows a variation of up to 1% in the lateral position, but only 0.4% for the PP31016 with an Al electrode. The air-to-water perturbation in the optimal scanning direction for both profiles and depth is most influenced by the radiation field, and only to a small extent the chamber geometry. The PP31016 geometry (shorter, larger radius) requires less total perturbation within the central axis of the field, but results in slightly larger variations off axis in the optimal scanning direction. Smaller spot sizes (0.6 mm FWHM) and sharper penumbras, compared to larger spot sizes (2 mm FWHM), result in larger perturbation starting in the penumbra. The longer geometries of the PP31006/14/15 exhibit in the non-optimal scanning direction large variations in total perturbation (p(tot) 1.201(4) (0.6 mm spot, 3 mm off axis, type A MC uncertainty) to 0.803(4) (5 mm off axis)) mainly due to volume perturbation. Therefore in IMRT settings, when the detector is not always in the optimal scanning direction, the PP31016 geometry requires less extreme perturbation (max p(tot) 1.130(3)) and shows less variation. However, these results suggest that small variations in positioning, spot size or MLC result in large differences in perturbation factors. Therefore even these 0.016 cm(3) ionization chambers are limited in their use for a field setting of 0.8 x 0.8 cm(2), as used in this investigation.

On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction.

The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry.

Monte Carlo modeling of the ModuLeaf miniature MLC for small field dosimetry and quality assurance of the clinical treatment planning system.

The purpose of this investigation was the verification of both the measured data and quality of the implementation of the add-on ModuLeaf miniature multileaf collimator (ML mMLC) into the clinical treatment planning system for conformal stereotactic radiosurgery treatment. To this end the treatment head with ML mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The 6 MV photon beams used in the setup were first benchmarked with a set of measurements. A total ML mMLC transmission of 1.13% of the 10 x 10 cm2 open field dose was measured and reproduced with the BEAMnrc/DOSXYZnrc code. Correspondence between calculated and measured output factors (OFs) was within 2%. Correspondence between MC and measured profiles was within 2% dose and 2 mm distance, only for the smallest 0.5 x 0.5 cm2 field the results were within 3% dose. In the next step, the MC model was compared with Gafchromic film measurements and Pinnacle(3) 7.4 f (convolution superposition algorithm) calculated dose distributions, using a gamma evaluation comparison, for a multi-beam patient setup delivered to a Lucytrade mark phantom. The gamma evaluation of the MC versus Gafchromic film resulted in 3.4% of points not fulfilling gamma