A. Lisbona

Validation of a personalized dosimetric evaluation tool (Oedipe) for targeted radiotherapy based on the Monte Carlo MCNPX code

Dosimetric studies are necessary for all patients treated with targeted radiotherapy. In order to attain the precision required, we have developed Oedipe, a dosimetric tool based on the MCNPX Monte Carlo code. The anatomy of each patient is considered in the form of a voxel-based geometry created using computed tomography (CT) images or magnetic resonance imaging (MRI). Oedipe enables dosimetry studies to be carried out at the voxel scale. Validation of the results obtained by comparison with existing methods is complex because there are multiple sources of variation: calculation methods (different Monte Carlo codes, point kernel), patient representations (model or specific) and geometry definitions (mathematical or voxel-based). In this paper, we validate Oedipe by taking each of these parameters into account independently. Monte Carlo methodology requires long calculation times, particularly in the case of voxel-based geometries, and this is one of the limits of personalized dosimetric methods. However, our results show that the use of voxel-based geometry as opposed to a mathematically defined geometry decreases the calculation time two-fold, due to an optimization of the MCNPX2.5e code. It is therefore possible to envisage the use of Oedipe for personalized dosimetry in the clinical context of targeted radiotherapy.

No impairment of quality of life 18 months after high-dose intensity-modulated radiotherapy for localized prostate cancer: a prospective study.

PURPOSE To determine prospectively intermediate-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS Fifty-five patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy). Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 6, and 18 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30(+3) and QLQ-PR25. RESULTS Median age was 73 years (range, 54-80 years). Risk categories were 18% low risk, 60% intermediate risk, and 22% high risk; 45% of patients received hormonal therapy (median duration, 6 months). The incidence of urinary and bowel toxicity immediately after IMRT was, respectively, 38% and 13% (Grade 2) and 2% and none (Grade 3); at 18 months it was 15% and 11% (Grade 2) and none (Grade 3). Significant worsening of QoL was reported at 2 months with regard to fatigue (+11.31, p = 1.10(-7)), urinary symptoms (+9.07, p = 3.10(-11)), dyspnea (+7.27, p = 0.008), and emotional (-7.02, p = 0.002), social (-6.36, p = 0.003), cognitive (-4.85, p = 0.004), and physical (-3.39, p = 0.007) functioning. Only fatigue (+5.86, p = 0.003) and urinary symptoms (+5.86, p = 0.0004) had not improved by 6 months. By 18 months all QoL scores except those for dyspnea (+8.02, p = 0.01) and treatment-related symptoms (+4.24, p = 0.01) had returned to baseline. These adverse effects were exacerbated by hormonal therapy. CONCLUSION High-dose IMRT with accurate positioning induces only a temporary worsening of QoL.

Voxeldose: A Computer Program for 3-D Dose Calculation in Therapeutic Nuclear Medicine

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.

Correction of count losses due to deadtime on a DST-XLi (SMVi-GE) camera during dosimetric studies in patients injected with iodine-131

In dosimetric studies performed after therapeutic injection, it is essential to correct count losses due to deadtime on the gamma camera. This note describes four deadtime correction methods, one based on the use of a standard source without preliminary calibration, and three requiring specific calibration and based on the count rate observed in different spectrometric windows (20%, 20% plus a lower energy window and the full spectrum of 50-750 keV). Experiments were conducted on a phantom at increasingly higher count rates to check correction accuracy with the different methods. The error was less than +7% with a standard source, whereas count-rate-based methods gave more accurate results. On the assumption that the model was paralysable, preliminary calibration allowed an observed count rate curve to be plotted as a function of the real count rate. The use of the full spectrum led to a 3.0% underestimation for the highest activity imaged. As count losses depend on photon flux independent of energy, the use of the full spectrum during measurement allowed scatter conditions to be taken into account. A protocol was developed to apply this correction method to whole-body acquisitions.

Helical tomotherapy for resected malignant pleural mesothelioma: dosimetric evaluation and toxicity.

This study evaluated adjuvant helical tomotherapy after extrapleural pneumonectomy ± neo-adjuvant chemotherapy in 24 patients with malignant pleural mesothelioma. Toxicity was judged acceptable despite 2 cases (8%) of suspected grade 5 pneumonitis. With a mean follow-up of 7 months, 5 patients had distant and 2 local and distant failure.

Comparison of Four Scatter Correction Methods for Patient Whole-Body Imaging during Therapeutic Trials with Iodine-131

Activity in regions of interest can be measured using serial whole‐body scintigraphic images to estimate the dose received by a patient after therapeutic injections. As scatter and attenuation introduce biases in quantitative measurements, these phenomena need to be corrected to allow accurate determination of tracer concentration.

Tomothérapie hélicoïdale : aspects techniques et applications cliniques

Helical tomotherapy is an innovative device combining with the same linac on board-imaging and IMRT facilities. The first national French evaluations, supported by National Institut of Cancer (INCa) are presented. Dosimetric characteristics as quality of homogeneity, cut-off outside target volumes allow IMRT treatments for large and complex volumes and a good organ at risk sparing. First comparative dosimetric studies are discussed.

Impact of Scatter and Attenuation Corrections for Iodine-131 Two-Dimensional Quantitative Imaging in Patients

This study assessed the impact of scatter and attenuation corrections on the estimated activity delivered to whole body and liver in five patients included in a radioimmunotherapy clinical trial. Before injection of the radiopharmaceutical, transmission images were acquired with the Transmission Attenuation Correction - Whole-body (SMVi-GEMS) prototype. Emission images were obtained in energy-indexed list mode at least four times after injection. 20% window and scatter-corrected images (Dual Energy Window-DEW and Triple Energy Window-TEW) were generated. Whole-body activity was calculated 1-h after injection (and compared with injected activity). Cumulated activities in whole body and liver were determined according to the geometric mean approach. The mean relative error made in estimations of whole-body activity at 1-h was 6.9+/-10.3% without corrections. Taking scatter into account led to underestimation, but reduced the influence of patient morphotype (-40.0+/-7.6% and -43.3+/-6.2% for DEW and TEW). Attenuation correction led to a large overestimation, whether used alone (155.2+/-39.0%) or associated with scatter correction (39.6+/-10.4% and 35.9+/-10.2% for DEW and TEW). Compared to the geometric mean alone, scatter correction led to a reduction of cumulated activities of around 45% for whole body and less than 30% for liver. Attenuation correction had a more marked impact, particularly for liver where estimated cumulated activity increased from 150 to 300%. Preliminary scatter correction limited the increase to 100% for DEW and 150% for TEW in liver and to 25% for both DEW and TEW in whole body. Although this would probably be different at the organ level, the calculation of whole-body activity without scatter and attenuation correction gave the lowest biases. But from a scientific point of view, this cannot be a satisfactory method. Attenuation correction has a greater impact than scatter correction. The association of both corrections is not sufficient to obtain accurate absolute quantification. Other factors limit planar quantification with iodine-131, notably auto-absorption of sources, septal penetration of high-energy photons through the collimator and superimposition of sources.

Validation of fast Monte Carlo dose calculation in small animal radiotherapy with EBT3 radiochromic films

In preclinical studies, the absorbed dose calculation accuracy in small animals is fundamental to reliably investigate and understand observed biological effects. This work investigated the use of the split exponential track length estimator (seTLE), a new kerma based Monte Carlo dose calculation method for preclinical radiotherapy using a small animal precision micro irradiator, the X-RAD 225Cx. Monte Carlo modelling of the irradiator with GATE/GEANT4 was extensively evaluated by comparing measurements and simulations for half-value layer, percent depth dose, off-axis profiles and output factors in water and water-equivalent material for seven circular fields, from 20 mm down to 1 mm in diameter. Simulated and measured dose distributions in cylinders of water obtained for a 360° arc were also compared using dose, distance-to-agreement and gamma-index maps. Simulations and measurements agreed within 3% for all static beam configurations, with uncertainties estimated to 1% for the simulation and 3% for the measurements. Distance-to-agreement accuracy was better to 0.14 mm. For the arc irradiations, gamma-index maps of 2D dose distributions showed that the success rate was higher than 98%, except for the 0.1 cm collimator (92%). Using the seTLE method, MC simulations compute 3D dose distributions within minutes for realistic beam configurations with a clinically acceptable accuracy for beam diameter as small as 1 mm.

Dosimetric Impact of Correcting Count Losses due to Deadtime in Clinical Radioimmunotherapy Trials Involving Iodine-131 Scintigraphy

This study describes the use of a new method for correcting count losses due to deadtime in the context of quantitative imaging of patients undergoing scintigraphy after a 4 GBq therapeutic injection of iodine-131. This method, based on measuring the count rate observed throughout the spectrum detected (50-750 keV), had been validated in a previous study and was applied here to 10 patients. Imaging was performed 3, 6, 8 and 10 days after injection. Whole-body images were acquired in six steps in energy-indexed list mode. Before reconstruction of the whole-body image, each step was processed to obtain an appropriate correction. Three days after injection, corrective factors ranged between 1.01 (feet) and 1.20 (liver), and the increase in whole-body activity was estimated at around 10%. The difference between whole-body activities calculated from images corrected for deadtime and those estimated by urine collection was around 1% when urine collection was complete. Correction for count losses led to an 11% increase in whole-body cumulated activity. These results indicate that it is possible to integrate this correction into dosimetric studies in order to allow count rate variations to be taken into account as a function of the regions imaged. Although the complexity of acquisitions in energy-indexed list mode limits the systematic use of this method, it can be simplified if corrections are made only for those steps in which the correction factor exceeds a threshold value. However, this implies a selection of the regions to be corrected. Another possibility consists in acquiring spectrometric images in several windows, which also allows correction for count losses.